Signal intensity changes of dentate nucleus on plain MR T1WI innasopharyngeal carcinoma patients after radiotherapy andmultiple injections of gadolinium-base contrast agent

Objective To observe changes of plain MR T1WI signal intensity of dentate nucleus in nasopharyngeal carcinoma patients after radiotherapy and multiple times of intravenous injection of gadolinium-based contrast agent(GBCA).Methods Fifty patients with pathologically confirmed nasopharyngeal carcinoma and received intensity-modulated radiotherapy were retrospectively enrolled as the nasopharyngeal carcinoma group,and 50 patients with other malignant tumors and without history of brain radiotherapy were retrospectively enrolled as the control group.All patients received yearly GBCA enhanced MR examinations for the nasopharynx or the head.T1WI signal intensities of the dentate nucleus and the pons on same plane were measured based on images in the year of confirmed diagnosis(recorded as the first year)and in the second to the fifth years.T1WI signal intensity ratio of year i(ranging from 1 to 5)was calculated with values of dentate nucleus divided by values of the pons(ΔSI i),while the percentage of relative changes of year j(ranging from 2 to 5)was calculated withΔSI j compared toΔSI 1(Rchange j).The values of these two parameters were compared,and the correlation ofΔSI and GBCA injection year-time was evaluated within each group.Results No significant difference of gender,age norΔSI 1 was found between groups(all P>0.05).The second to the fifth yearΔSI and Rchange in nasopharyngeal carcinoma group were all higher than those in control group(all P<0.05).Within both groups,ΔSI was positively correlated with GBCA injection year-time(both P<0.05).Conclusion Patients with nasopharyngeal carcinoma who underwent radiotherapy and multiple times of intravenous injection of GBCA tended to be found with gradually worsening GBCA deposition in dentate nucleus,for which radiotherapy might be a risk factor.

3-Methyladenine potentiates paclitaxel-induced apoptosis and phosphorylation of cyclin-dependent kinase 1 at thr161 in nasopharyngeal carcinoma cell

Background:Nasopharyngeal carcinoma(NPC)exhibits a significant prevalence in the southern regions of China,and paclitaxel(PTX)is frequently employed as a medication for managing advanced NPC.However,drug resistance is typically accompanied by a poor prognosis.Exploring the synergistic potential of combining multiple chemotherapeutic agents may represent a promising avenue for optimizing treatment efficacy.Methods:This study investigated whether 3-Methyladenine(3-MA)could potentiated the effect of PTX and its potential molecular mechanism.Samples were divided into the following categories:Negative control(NC)with the solvent dimethyl sulfoxide(DMSO,0.5%v/v),PTX(400 nM),3-MA(4 mM),and PTX(400 nM)+3-MA(4 mM).The viability of NPC cells was assessed using both the cell counting kit-8(CCK-8)assay and the colony formation assay.Microscopic observation was performed to identify morphological cell changes.Flow cytometry was used to assess cell cycle status,mitochondrial membrane potential(MMP),and apoptotic cells.Western blotting was conducted to quantify the protein expression.Results:3-MA enhanced PTX-specific inhibition of NPC cell proliferation.PTX,either alone or in combination with 3-MA,caused cell cycle halt at the G2/M phase in the majority of NPC cells,and the combination treatment of PTX with 3-MA induced a higher rate of NPC cell death compared to PTX alone.Western blotting results revealed the combination of PTX with 3-MA heightened activation of cyclin-dependent kinase 1(CDK1),a key molecule in shifting cells from mitotic arrest to apoptosis,led to a reduction in Myeloid Cell Leukemia 1(MCL-1)expression and an increase in Poly(ADP-ribose)polymerase(PARP)cleavage.Conclusion:The concurrent administration of PTX with 3-MA effectively enhances PTX’s inhibitory impact on NPC and activates the apoptosis signal regulated by CDK1.

Changing Nasopharyngeal Carcinoma Survival in Southern China during 2000-2015: Results of a Retrospective Cohort Study

Objective: Around 50% of new nasopharyngeal carcinoma (NPC) cases come from China. The present study aimed to update the surveillance of NPC survival in southern China, and investigate the survival disparities between sexes within this patient population. Methods: Patients diagnosed with primary and invasive NPC between 2000 and 2015 were included in this study. Data on demographics, diagnosis, and follow-up to December 2020 were collected. Patients were stratified by diagnosis period, sex, and age at diagnosis. Survival analysis employed cohort and Life Table methods, Kaplan-Meier curves, log-rank tests, and Cox regression. Results: The study included 32,901 patients, of whom 69.6% were males. The overall 5-year survival rate rose from 69.6% in 2000-2003 to 83.3% in 2013-2015, with a consistent average increase of 3.3% every 3 years. For males, the 5-year survival rate increased from 66.3% to 82.0%, faster than females. Kaplan-Meier curves demonstrated a significantly higher survival rate for females than males, and subgroup analysis confirmed this advantage. The Cox proportional hazards model confirmed the lower mortality risk for females (HR 0.75, 95% CI: 0.71 - 0.78), patients with younger ages at diagnosis, and patients diagnosed in more recent years (All P Conclusions: The 5-year survival rate for NPC patients in southern China has significantly and steadily improved from 2000 to 2015, indicating the improved quality of cancer care in China. The survival advantage of female patients is not limited to younger patients but is also observed in postmenopausal patients, despite the gradual narrowing of the gender gap.

Downregulation of MUC1 Inhibits Proliferation and Promotes Apoptosis by Inactivating NF-κB Signaling Pathway in Human Nasopharyngeal Carcinoma

Objective To investigate the effect of mucin 1(MUC1)on the proliferation and apoptosis of nasopharyngeal carcinoma(NPC)and its regulatory mechanism.Methods The 60 NPC and paired para-cancer normal tissues were collected from October 2020 to July 2021 in Quanzhou First Hospital.The expression of MUC1 was measured by real-time quantitative PCR(qPCR)in the patients with PNC.The 5-8F and HNE1 cells were transfected with siRNA control(si-control)or siRNA targeting MUC1(si-MUC1).Cell proliferation was analyzed by cell counting kit-8 and colony formation assay,and apoptosis was analyzed by flow cytometry analysis in the 5-8F and HNE1 cells.The qPCR and ELISA were executed to analyze the levels of TNF-αand IL-6.Western blot was performed to measure the expression of MUC1,NFкB and apoptosis-related proteins(Bax and Bcl-2).Results The expression of MUC1 was up-regulated in the NPC tissues,and NPC patients with the high MUC1 expression were inclined to EBV infection,growth and metastasis of NPC.Loss of MUC1 restrained malignant features,including the proliferation and apoptosis,downregulated the expression of p-IкB、p-P65 and Bcl-2 and upregulated the expression of Bax in the NPC cells.Conclusion Downregulation of MUC1 restrained biological characteristics of malignancy,including cell proliferation and apoptosis,by inactivating NF-κB signaling pathway in NPC.

Isotropic volumetric MRI for displaying cranial perineural spread of cranial nerve in nasopharyngeal carcinoma

Objective To observe the value of isotropic volumetric MRI for displaying perineural spread(PNS)of cranial nerve(CN)in nasopharyngeal carcinoma.Methods Eighty-seven patients with pathologically proven nasopharyngeal carcinoma were prospectively enrolled.MR scanning,including three-dimensional liver acquisition with volume acceleration-flexible(3D LAVA_Flex)image,T2WI with fat suppression(T2WI-FS),T1WI,contrast enhancement(CE)T1WI-FS of nasopharynx and neck region were performed.The displaying rates of CN PNS were evaluated and compared between 3D LAVA_Flex and T2WI-FS,T1WI,CE-T1WI-FS at patient level,CN group level and neural level,respectively.Results The displaying rate of CN PNS in all 87 nasopharyngeal carcinoma patients by 3D LAVA_Flex sequence was 49.43%(43/87),higher than that of conventional MRI(30/87,34.48%,P=0.001).Among 59 patients with advanced nasopharyngeal carcinoma diagnosed with conventional sequences,the displaying rate of CN PNS was 71.19%(42/59)by 3D LAVA-Flex sequence,higher than that of conventional MRI(30/59,50.85%,P=0.001).At both patient level and posterior CN level,significant differences of the displaying rate of CN PNS were found between 3D LAVA-Flex sequence and T2WI-FS,T1WI,CE-T1WI-FS,while at CN level,the displaying rates of mandibular nerve PNS,CNⅨ—ⅪPNS in jugular foramen(P<0.05)and CNⅨ—ⅫPNS in carotid space of 3D LAVA_Flex sequence were all significantly higher than that of T2WI-FS,T1WI and CE-T1WI-FS(all P<0.05),of PNS of CNⅢ—Ⅴin cavernous sinus were higher than that of T2WI-FS(P<0.05),while of PNS of hypoglossal nerve were significantly higher than that of T2WI-FS and T1WI(both P<0.05).Conclusion 3D LAVA_Flex sequence could be used to effectively display CN PNS of nasopharyngeal carcinoma.

Treatment of nasopharyngeal carcinoma and prevention of nonalcoholic Wernicke’s disease:A case report and review of literature

BACKGROUND Wernicke encephalopathy is a neurological disorder caused by thiamine deficiency,commonly seen in alcoholic populations but also involving other circumstances that may lead to thiamine deficiency.The recognition of Wernicke encephalopathy often depends on clinicians’keen ability to detect its typical triad of features;however,most cases do not present with the full constellation of signs,which complicates the timely identification of Wernicke encephalopathy.CASE SUMMARY This case report describes a patient with nasopharyngeal carcinoma who developed abnormal ocular function and ataxia following concurrent chemoradiotherapy,without a history of alcohol abuse.With the aid of radiological examinations,he received a timely diagnosis and treatment;however,his symptoms did not fully resolve during follow-up.CONCLUSION For patients with malignant tumors exhibiting neurological symptoms,clinicians should consider the possibility of Wernicke encephalopathy and provide prophylactic thiamine therapy.

Predicting distant metastasis in nasopharyngeal carcinoma using gradient boosting tree model based on detailed magnetic resonance imaging reports

BACKGROUND Development of distant metastasis(DM)is a major concern during treatment of nasopharyngeal carcinoma(NPC).However,studies have demonstrated im-proved distant control and survival in patients with advanced NPC with the addition of chemotherapy to concomitant chemoradiotherapy.Therefore,precise prediction of metastasis in patients with NPC is crucial.AIM To develop a predictive model for metastasis in NPC using detailed magnetic resonance imaging(MRI)reports.METHODS This retrospective study included 792 patients with non-distant metastatic NPC.A total of 469 imaging variables were obtained from detailed MRI reports.Data were stratified and randomly split into training(50%)and testing sets.Gradient boosting tree(GBT)models were built and used to select variables for predicting DM.A full model comprising all variables and a reduced model with the top-five variables were built.Model performance was assessed by area under the curve(AUC).RESULTS Among the 792 patients,94 developed DM during follow-up.The number of metastatic cervical nodes(30.9%),tumor invasion in the posterior half of the nasal cavity(9.7%),two sides of the pharyngeal recess(6.2%),tubal torus(3.3%),and single side of the parapharyngeal space(2.7%)were the top-five contributors for predicting DM,based on their relative importance in GBT models.The testing AUC of the full model was 0.75(95%confidence interval[CI]:0.69-0.82).The testing AUC of the reduced model was 0.75(95%CI:0.68-0.82).For the whole dataset,the full(AUC=0.76,95%CI:0.72-0.82)and reduced models(AUC=0.76,95%CI:0.71-0.81)outperformed the tumor node-staging system(AUC=0.67,95%CI:0.61-0.73).CONCLUSION The GBT model outperformed the tumor node-staging system in predicting metastasis in NPC.The number of metastatic cervical nodes was identified as the principal contributing variable.

Integrated strategies for chemotherapy cycles in nasopharyngeal carcinoma patients: Real-world data from two epidemic centers guiding decision-making

objective:Two cycles of induction chemotherapy(IC)followed by 2 cycles of platinum-based concurrent chemoradiotherapy(CCRT)(2IC+2CCRT)for locoregionally advanced nasopharyngeal carcinoma(LA-NPC)is widely adopted but not evidence-confirmed.This study aimed to determine the clinical value of 2IC+2CCRT regarding efficacy,toxicity and cost-effectiveness.Methods:This real-world study from two epidemic centers used propensity score matching(PSM)and inverse probability of treatment weighting(IPTW)analyses.The enrolled patients were divided into three groups based on treatment modality:Group A(2IC+2CCRT),Group B(3IC+2CCRT or 2IC+3CCRT)and Group C(3IC+3CCRT).Long-term survival,acute toxicities and cost-effectiveness were compared among the groups.We developed a prognostic model dividing the population into high-and low-risk cohorts,and survivals including overall survival(OS),progression-free survival(PFS),distant metastasis-free survival(DMFS)and locoregional relapse-free survival(LRRFS)were compared among the three groups according to certain risk stratifications.Results:Of 4,042 patients,1,175 were enrolled,with 660,419,and 96 included in Groups A,B and C,respectively.Five-year survivals were similar among the three groups after PSM and confirmed by IPTW.Grade 3-4 neutropenia and leukocytopenia were significantly higher in Groups C and B than in Group A(52.1%vs.41.5%vs.25.2%;41.7%vs.32.7%vs.25.0%)as were grade 3-4 nausea/vomiting and oral mucositis(29.2%vs.15.0%vs.6.1%;32.3%vs.25.3%vs.18.0%).Cost-effective analysis suggested that 2IC+2CCRT was the least expensive,while the health benefits were similar to those of the other groups.Further exploration showed that 2IC+2CCRT tended to be associated with a shorter PFS in high-risk patients,while 3IC+3CCRT potentially contributed to poor PFS in low-risk individuals,mainly reflected by LRRFS.Conclusions:In LA-NPC patients,2IC+2CCRT was the optimal choice regarding efficacy,toxicity and costeffectiveness;however,2IC+2CCRT and 3IC+3CCRT probably shortened LRRFS in high-and low-risk populations,respectively.

Surgical resection of a solitary liver metastasis from nasopharyngeal carcinoma: a case report

BACKGROUND: Nasopharyngeal carcinoma (NPC) has a propensity to develop distant metastases at a high rate and with poor prognosis. Metastatic sites are usually multifocal and involve bones, lungs, liver and distant lymph nodes. Management of metastatic disease is essentially palliative and is based on chemotherapy. METHODS: A 50-year-old man with a solitary liver metastasis from a newly diagnosed NPC was treated by segmentectomy. Prior to surgery, neoadjuvant chemo therapy followed by concurrent chemoradiotherapy was administered. RESULTS: Complete remission of the primary disease was achieved, although the size of the hepatic lesion was increased. After resection of the liver metastasis, no signs of local or distant recurrence was noted during the 6-month follow up. CONCLUSION: Although surgical treatment has a limited role in metastatic NPC, there are rare cases of localized disease with a reasonable outcome after resection.

KIF15, a key regulator of nasopharyngeal carcinoma development mediated by the P53 pathway

Background:Kinesin family member 15(KIF15)is a protein that regulates cell mitosis and plays an important role in the development and progression of several types of human cancers.However,the role of KIF15 in the development of nasopharyngeal cancer(NPC)is still unclear.Methods:The differential expression of KIF15 in NPC and para-carcinoma tissues was evaluated based on data collected from Gene Expression Omnibus(GEO)database and immunohistochemical analysis of clinical specimens collected from a patient cohort.Cell lines 5-8F and CNE-2Z were selected for the construction of KIF15‑knockdown cell models.CCK8 assay,flow cytometry,wound healing,Transwell and clone formation assays were used to detect the proliferation,apoptosis,migration,invasion and colony formation of NPC cells in vitro.A mouse xenograft model and the tail intravenous mouse distant transfer model were constructed for in vivo study.Furthermore,the potential molecular mechanisms underlying the effects of KIF15 were explored through western blot analysis,and several in vitro and in vivo functional assays were performed to explore its role in NPC.Results:The results revealed significantly higher expression of KIF15 in NPC tissues compared to para-carcinoma tissues.High levels of KIF15 expression were also associated with short overall survival(OS)and progression-free survival(PFS).Knockdown of the KIF15 gene led to a cell cycle arrest in the growth 2(G2)phase,inhibition of cell proliferation,migration,invasion,colony formation,and enhanced cell apoptosis.The in vivo murine xenograft experiments showed that down-regulation of the KIF15 gene could inhibit tumor growth and reduce the risk of liver and lung metastasis in NPC.Moreover,the evaluation of the molecular pathway showed that the mitogen-activated protein kinase/P53 pathways might be involved in the KIF15-induced regulation of NPC.Rescue assays indicated that Pifithrin-αcould counteract the pro-proliferative and pro-apoptotic effects mediated by KIF15.Conclusion:This work indicated that KIF15 overexpression accelerated the progression of NPC and promoted the development of distant metastases.Therefore,KIF15 may have an important role as a prognostic indicator and a potential drug target for the treatment of NPC.

SIRT2 interacts with DDX24 to promote nasopharyngeal carcinoma growth

Background:Nasopharyngeal carcinoma(NPC)is one of the most prevalent cancers in Southeast Asia.Sirtuin 2(SIRT2)is a member of the NAD+-dependent deacetylase family and has been shown to play important roles in numerous biological processes.However,Its function in NPC remains uncertain.The primary aim of this study is to clarify the role of SIRT2 in NPC.Methods:In this research,we examined the effect of SIRT2 silencing on NPC cell proliferation and colony formation using vitro NPC cell lines.Co-immunoprecipitation and mass spectrometry was applied to identify SIRT2-interacting proteins in NPC cells.Results:In comparison to nasopharyngeal epithelial NP69 cells,SIRT2 was up-regulated in multiple NPC cell lines,particularly in CNE2 cells.SIRT2 knockdown abrogated CNE2 cell proliferation and colony formation,whereas SIRT2 overexpression promoted HNE1 cell proliferation and colony formation.The SIRT2-interacting proteins were gathered in gene expression and regulation processes including RNA processing and translation.Among the SIRT2-interacting proteins,there were multiple DEAD-box(DDX)family members.Of note,silencing of DDX24 phenocopied the effect of SIRT2 knockdown on NPC growth.Overexpression of DDX24 restored SIRT2-depleted CNE2 cells to proliferative and colony formation.Conclusions:Our study indicates that SIRT2 can interact with DDX24 to enhance NPC growth.The clinical relevance of SIRT2 and DDX24 in NPC warrants further investigation.

Effects of Cisplatin and Metformin on Proliferation of Nasopharyngeal Carcinoma SUNE-1 Cells

[Objectives]This study was conducted to investigate the effects of different concentrations of cisplatin and metformin on the growth and proliferation of nasopharyngeal carcinoma SUNE-1 cells.[Methods]The concentrations of cisplatin were set as 2.5,5.0,10.0,25.0,40.0μg/mL,and those of metformin were set as 0.625,1.25,2.5,5,10,and 20 mmol/L.After 48 h of intervention in nasopharyngeal carcinoma SUNE-1 cells,the proliferation inhibitory rate and the median inhibitory concentration(IC_(50))of SUNE-1 cells were measured by the CCK-8 method.[Results]It was found that different concentrations of cisplatin and metformin all had an inhibitory effect on the proliferation of SUNE-1 cells,and the inhibitory effect became more significant with the increase of concentration.The IC_(50)values of cisplatin and metformin were 43.57μg/mL and 6.855 mmol/L,respectively.[Conclusions]Cisplatin and metformin inhibited the proliferation of SUNE-1 cells in a concentration-dependent manner,providing a theoretical guidance for the clinical treatment of nasopharyngeal carcinoma.

Comparative Study between Patients Treated with Conventional Radiotherapy and IMRT with Chemotherapy for Stage III - IVA Nasopharyngeal Carcinoma: A Single Institution Retrospective Report

Introduction: Nasopharyngeal carcinomas are the most radiation-sensitive tumours, and radiotherapy alone provides better local control. Objectives: To evaluate the clinical efficacy and acute and late toxicities of two different treatment regimens for locally advanced nasopharyngeal carcinoma. Methods: From 2014 to 2017, 150 cases of stage III and 68 cases of stage IVA nasopharyngeal carcinoma were treated. Of these, 137 received conventional radiotherapy plus chemotherapy, and 81 received intensity-modulated radiotherapy plus chemotherapy. Chemotherapy was given either as induction, concurrent or adjuvant therapy. Survival rates were calculated according to Kaplan Meier and compared with the Log-rank test. The RTOG or EORTC criteria were used to assess acute and late toxicities. Results: The median follow-up time was 21.5 months, and the 2-year locoregional relapse-free survival, distant metastases-free survival, and overall survival rates in the conventional radiotherapy plus chemotherapy group were 76%, 71% and 77%, respectively;in the intensity-modulated radiotherapy plus chemotherapy group, they were 97%, 84%, and 100%, respectively. The difference in survival between the two groups was significant (χ2 = 5.06, P = 0.028). The incidence of grade 2 and 3 xerostomia one year after radiotherapy was 45.1% and 30.9% versus 33.3% and 0%. Conclusion: Compared with conventional radiotherapy plus chemotherapy, intensity-modulated radiotherapy plus chemotherapy offers better locoregional relapse-free survival and overall survival in patients with stage III and IVA nasopharyngeal carcinoma, and may significantly reduce the occurrence of radiation-induced xerostomia.

Nasopharyngeal carcinoma with synchronous breast metastasis:A case report

BACKGROUND Recent reports have described cases of metachronous breast metastasis in patients with nasopharyngeal carcinoma.However,no similar cases of synchronous breast metastasis have been reported,and evidence that can be used to support the clinical diagnosis of stage IV nasopharyngeal carcinoma in patients with concurrent breast metastasis remains lacking.Therefore,additional evidence is required to elucidate the clinical characteristics of this condition and aid in the development of optimal management strategies.CASE SUMMARY We report the case of a 46-year-old woman who visited our hospital with a right breast mass as the first symptom.The first pathological biopsy report suggested triple-negative breast invasive carcinoma.Subsequent imaging revealed a nasopharyngeal mass.Further puncture biopsy of the nasopharyngeal mass,molecular pathological Epstein–Barr virus in situ hybridization,and immunohistochemistry confirmed the diagnosis of nasopharyngeal carcinoma with breast metastasis.The patient did not undergo a mastectomy and achieved complete remission after chemotherapy and radiotherapy.She continued to receive oral chemotherapy as maintenance therapy and experienced no recurrence or metastasis during the 6-month follow-up period.CONCLUSION This case report suggests that breast specialists should carefully rule out secondary breast cancers when diagnosing and treating breast masses.Furthermore,clinicians should aim to identify the pathological type of the tumor to obtain the most accurate diagnosis and prevent excessive diagnosis and treatment.

Three-Dimensional Conformal and Intensity Modulated Dynamic Radiotherapy in Juvenile Nasopharyngeal Angiofibroma

Objective: Juvenile Nasopharyngeal Angiofibroma (JNA) is a benign neoplasm with a high vascularity component, greater craniofacial involvement in adolescent patients, and aggressive local behaviour. In unresectable patients, radiotherapy is a therapeutic option for local control. Our aim in this study was to analyze the clinical benefit and local control provided by two modalities of radiotherapy: the Three-Dimensional Conformal (3DC) technique and volumetric modulated arc therapy (VMAT), applied to pediatric patients with JNA considered unresectable and non-recurrent. Methods: In retrospective study, the information was recorded from pediatric patients with a diagnosis of non-recurrent and unresectable JNA treated with radiotherapy at the Oncology Hospital of the National Medical Center SXXI of Mexico City, from March 2010 to March 2021. Radiotherapy management and its association with clinical outcomes of tumour control, and symptoms were assessed. In addition, an evaluation of acute and chronic toxicity was performed. Results: It was found that the median age was 14 years. 9 patients (37.5%) underwent 3DC and 15 (62.5%) VMAT. In terms of local control, and progression-free survival, we did not find significant difference between radiotherapy modalities (p ≤ 0.57). Acute toxicity for both modalities presented statistical differences for radio epithelitis (p = 0.03). Only Grade I and II radiation-induced acute toxicity was observed. Regarding chronic toxicity, statistical significance was observed for craniofacial hypoplasia, in relation to its absence in the VMAT group (p = 0.001). Conclusion: The VMAT presents improvements in dosimetry parameters that improve patient toxicity. In both techniques adequate tumour control was observed, however, the rarity of the disease is a limitation to establish the most appropriate therapeutic technique.

Massive Rhinorrhea as a Complication of COVID-19 Nasopharyngeal Swab

The nasopharyngeal swab for COVID-19 testing is generally considered safe;however, it is primarily performed by staff that may not completely understand the anatomy of the nasal cavity and nasopharynx. We report the treatment of a 48-year-old man who developed unilateral left rhinorrhea after a nasopharyngeal swab sample. It is aimed to draw attention to this complication that can be prevented with the appropriate technique during nasopharyngeal swab sampling.

Future Changes in Various Cold Surges over China in CMIP6 Projections

Cold surges(CSs)often occur in the mid-latitude regions of the Northern Hemisphere and have enormous effects on socioeconomic development.We report that the occurrences of CSs and persistent CSs(PCSs)have rebounded since the 1990s,but the trends related to the frequencies of strong CSs(SCSs)and extreme CSs(ECSs)changed from increasing to decreasing after 2000.The highest-ranked model ensemble approach was used to project the occurrences of various CSs under the SSP1-2.6,SSP2-4.5,and SSP5-8.5 scenarios.The frequencies of the total CSs show overall decreasing trends.However,under the SSP1-2.6 scenario,slight increasing trends are noted for SCSs and ECSs in China.Atmospheric circulations that are characterized by an anomalous anticyclonic circulation with a significantly positive 500-hPa geopotential height(Z500)anomaly at high latitudes along with significant negative anomalies in China were favorable for cold air intrusions into China.In addition,the frequencies of all CS types under the SPP5-8.5 scenario greatly decreased in the long term(2071-2100),a finding which is thought to be related to negative SST anomalies in the central and western North Pacific,differences in sea level pressure(SLP)between high-and mid-latitude regions,and a weaker East Asian trough.In terms of ECSs,the decreasing trends observed during the historical period were maintained until 2024 under the SSP1-2.6 scenario.Compared to the SSP1-2.6 scenario,the Z500 pattern showed a trend of strengthened ridges over the Ural region and northern East Asia and weakened troughs over Siberia(60°-90°E)under the SSP2-4.5 and SSP5-8.5 scenarios,contributing to the shift to increasing trends of ECSs after 2014.

Trend of Storm Surge Induced by Typical Landfall Super Typhoons During 1975–2021 in the Eastern China Sea

Climate change affects the activity of global and regional tropical cyclones(TCs).Among all TCs,typical super typhoons(STYs)are particularly devastating because they maintain their intensity when landing on the coast and thus cause casualties,economic losses,and environmental damage.Using a 3D tidal model,we reconstructed the typhoon(TY)wind field to simulate the storm surge induced by typical STYs.The TY activity was then analyzed using historical data.Results showed a downtrend of varying degrees in the annual frequency of STYs and TCs in the Western North Pacific(WNP)Basin,with a significant trend change observed for TCs from 1949 to 2021.A large difference in the interannual change in frequency was found between STYs and TCs in the WNP and Eastern China Sea(ECS).Along the coast of EC,the frequency of landfall TCs showed a weak downtrend,and the typical STYs showed reverse micro growth with peak activity in August.Zhejiang,Fujian,and Taiwan were highly vulnerable to the frontal hits of typical STYs.Affected by climate change,the average lifetime maximum intensity(LMI)locations and landfall locations of typical STYs in the ECS basin showed a significant poleward migration trend.In addition,the annual average LMI and accumulated cyclone energy showed an uptrend,indicating the increasing severity of the disaster risk.Affected by the typical STY activity in the ECS,the maximum storm surge area also showed poleward migration,and the coast of North China faced potential growth in high storm surge risks.

Exploration of standard dosage for GnRH antagonist protocol and dosage adjustments after premature luteinizing hormone surge

The gonadotropin-releasing hormone (GnRH) antagonist protocol has emerged as an efficacious alternative to the GnRH agonist protocol for controlled ovarian hyperstimulation (COH) during in vitro fertilization (IVF) cycles, and has been demonstrated applicability in infertile female patients with diverse ovarian responses. While the clinical implementation of the antagonist COH protocol has achieved widespread consensus, opportunities for refinement persist. Therefore, this review article focuses on the advantages and disadvantages of GnRH antagonist protocol, the selection of optimal standard doses, and the strategies for adjusting antagonist doses after the premature luteinizing hormone (LH) surge, aiming to provide more reasonable and scientific recommendations for the application of this scheme.

A typhoon-induced storm surge numerical model with GPU acceleration based on an unstructured spherical centroidal Voronoi tessellation grid

Storm surge is often the marine disaster that poses the greatest threat to life and property in coastal areas.Accurate and timely issuance of storm surge warnings to take appropriate countermeasures is an important means to reduce storm surge-related losses.Storm surge numerical models are important for storm surge forecasting.To further improve the performance of the storm surge forecast models,we developed a numerical storm surge forecast model based on an unstructured spherical centroidal Voronoi tessellation(SCVT)grid.The model is based on shallow water equations in vector-invariant form,and is discretized by Arakawa C grid.The SCVT grid can not only better describe the coastline information but also avoid rigid transitions,and it has a better global consistency by generating high-resolution grids in the key areas through transition refinement.In addition,the simulation speed of the model is accelerated by using the openACC-based GPU acceleration technology to meet the timeliness requirements of operational ensemble forecast.It only takes 37 s to simulate a day in the coastal waters of China.The newly developed storm surge model was applied to simulate typhoon-induced storm surges in the coastal waters of China.The hindcast experiments on the selected representative typhoon-induced storm surge processes indicate that the model can reasonably simulate the distribution characteristics of storm surges.The simulated maximum storm surges and their occurrence times are consistent with the observed data at the representative tide gauge stations,and the mean absolute errors are 3.5 cm and 0.6 h respectively,showing high accuracy and application prospects.